rs1132200

Variant names:

• chr3-119431989-C-A
• rs1132200
• NM_018266.3:c.1459G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-119431989-C-A
• chr3-119431989-C-G
• chr3-119431989-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018266.3(TMEM39A):​c.1459G>T​(p.Ala487Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM39A NM_018266.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• Publications: 0 publications found

Genes affected

TMEM39A (HGNC:25600): (transmembrane protein 39A) Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of viral genome replication. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16436675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM39A	NM_018266.3	c.1459G>T	p.Ala487Ser	missense_variant	Exon 9 of 9	ENST00000319172.10	NP_060736.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM39A	ENST00000319172.10	c.1459G>T	p.Ala487Ser	missense_variant	Exon 9 of 9	1	NM_018266.3	ENSP00000326063.5
TMEM39A	ENST00000473684.5	n.*497G>T		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000420432.1
TMEM39A	ENST00000473684.5	n.*497G>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000420432.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1430834 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 710282

African (AFR) AF: 0.00 AC: 0 AN: 32860

American (AMR) AF: 0.00 AC: 0 AN: 42958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25404

East Asian (EAS) AF: 0.00 AC: 0 AN: 38768

South Asian (SAS) AF: 0.00 AC: 0 AN: 80930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093318

Other (OTH) AF: 0.00 AC: 0 AN: 58854

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.10
Sift	Benign	0.030	D
Sift4G	Benign	0.069	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.086		Gain of methylation at K486 (P = 0.083);
MVP		0.068
MPC		0.33
ClinPred		0.48	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.086
gMVP		0.36
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1132200; hg19: chr3-119150836;